{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:27:27Z","timestamp":1789273647338,"version":"build-2803163510"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This study reports for the first time the isolation of four diterpenoid compounds: 15-Hydroxy-12-oxo-abietic acid (1), 12\u03b1-hydroxyabietic acid (2), (\u2212)-Jolkinolide E (3), and 15-Hydroxydehydroabietic acid (4) from Clinopodium bolivianum (C. bolivianum). The findings demonstrate that both the dichloromethane\/methanol (DCMECB) extract of C. bolivianum and the isolated compounds exhibit significant anti-inflammatory (inhibition of NF-\u03baB activation), antibacterial (primarily against Gram-positive bacteria), and anti-biofilm (primarily against Gram-negative bacteria) activities. Among the isolated diterpenes, compounds 3 and 4 showed notable anti-inflammatory effects, with IC50 values of 17.98 \u03bcM and 23.96 \u03bcM for compound 3, and 10.79 \u03bcM and 17.37 \u03bcM for compound 4, in the HBEC3-KT and MRC-5 cell lines. Regarding their antibacterial activity, compounds 3 and 4 were particularly effective, with MIC values of 0.53\u20131.09 \u03bcM and 2.06\u20134.06 \u03bcM, respectively, against the S. pneumoniae and S. aureus Gram-positive bacteria. Additionally, these compounds demonstrated significant anti-biofilm and anti-quorum sensing activities, especially against Gram-negative bacteria (H. influenzae and L. pneumophila). We also explain how compound 3 (BIC = 1.50\u20132.07 \u03bcM, Anti-QS = 0.31\u20130.64 \u03bcM) interferes with quorum sensing due to its structural homology with AHLs, while compound 4 (BIC = 4.65\u20137.15 \u03bcM, Anti-QS = 1.21\u20132.39 \u03bcM) destabilises bacterial membranes due to the presence and position of its hydroxyl groups. These results support the traditional use of C. bolivianum against respiratory infections caused by both Gram-positive and Gram-negative bacteria. Furthermore, given the increasing antibiotic resistance and biofilm formation by these bacteria, there is a pressing need for the development of new, more active compounds. In this context, compounds 3 and 4 isolated from C. bolivianum offer promising potential for the development of a library of new, more potent, and selective drugs.<\/jats:p>","DOI":"10.3390\/pharmaceutics16081094","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"1094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti-Inflammatory, Antibacterial, Anti-Biofilm, and Anti-Quorum Sensing Activities of the Diterpenes Isolated from Clinopodium bolivianum"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-3909","authenticated-orcid":false,"given":"Luis","family":"Apaza Ticona","sequence":"first","affiliation":[{"name":"Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Department of Organic Chemistry, Faculty of Sciences, University Aut\u00f3noma of Madrid, Cantoblanco, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Mart\u00ednez Noguer\u00f3n","sequence":"additional","affiliation":[{"name":"Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3526-5151","authenticated-orcid":false,"given":"Javier","family":"S\u00e1nchez S\u00e1nchez-Corral","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University Aut\u00f3noma of Madrid, Cantoblanco, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Montoto Lozano","sequence":"additional","affiliation":[{"name":"Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monserrat","family":"Ortega Domenech","sequence":"additional","affiliation":[{"name":"Dr. Goya An\u00e1lisis S.L., Alcal\u00e1 de Henares, 28805 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"220150","DOI":"10.1183\/16000617.0150-2022","article-title":"Respiratory infections","volume":"31","author":"Niederman","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.resinv.2021.09.009","article-title":"Atypical pneumonia: Pathophysiology, diagnosis, and treatment","volume":"60","author":"Miyashita","year":"2022","journal-title":"Respir. 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